Molecular profiling of the hippocampus of children with autism spectrum disorder.

Autor: Rexrode LE; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA., Hartley J; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA., Showmaker KC; Dasomics LLC, Madison, MS, USA., Challagundla L; Department of Cell and Molecular Biology, University of Mississippi Medical School, Jackson, MS, USA., Vandewege MW; Dasomics LLC, Madison, MS, USA., Martin BE; Department of Cell and Molecular Biology, University of Mississippi Medical School, Jackson, MS, USA., Blair E; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA., Bollavarapu R; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA., Antonyraj RB; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA., Hilton K; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA., Gardiner A; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA., Valeri J; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA.; Program in Neuroscience, University of Mississippi Medical School, Jackson, MS, USA., Gisabella B; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA.; Program in Neuroscience, University of Mississippi Medical School, Jackson, MS, USA., Garrett MR; Department of Cell and Molecular Biology, University of Mississippi Medical School, Jackson, MS, USA., Theoharides TC; Institute of Neuro-Immune Medicine, Nova Southeastern University, Clearwater, FL, USA.; Department of Immunology, Tufts University School of Medicine, Boston, MA, USA., Pantazopoulos H; Department of Psychiatry and Human Behavior, University of Mississippi Medical School, Jackson, MS, USA. cpantazopoulos@umc.edu.; Program in Neuroscience, University of Mississippi Medical School, Jackson, MS, USA. cpantazopoulos@umc.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Jul; Vol. 29 (7), pp. 1968-1979. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1038/s41380-024-02441-8
Abstrakt: Several lines of evidence point to a key role of the hippocampus in Autism Spectrum Disorders (ASD). Altered hippocampal volume and deficits in memory for person and emotion related stimuli have been reported, along with enhanced ability for declarative memories. Mouse models have demonstrated a critical role of the hippocampus in social memory dysfunction, associated with ASD, together with decreased synaptic plasticity. Chondroitin sulfate proteoglycans (CSPGs), a family of extracellular matrix molecules, represent a potential key link between neurodevelopment, synaptic plasticity, and immune system signaling. There is a lack of information regarding the molecular pathology of the hippocampus in ASD. We conducted RNAseq profiling on postmortem human brain samples containing the hippocampus from male children with ASD (n = 7) and normal male children (3-14 yrs old), (n = 6) from the NIH NeuroBioBank. Gene expression profiling analysis implicated molecular pathways involved in extracellular matrix organization, neurodevelopment, synaptic regulation, and immune system signaling. qRT-PCR and Western blotting were used to confirm several of the top markers identified. The CSPG protein BCAN was examined with multiplex immunofluorescence to analyze cell-type specific expression of BCAN and astrocyte morphology. We observed decreased expression of synaptic proteins PSD95 (p < 0.02) and SYN1 (p < 0.02), increased expression of the extracellular matrix (ECM) protease MMP9 (p < 0.03), and decreased expression of MEF2C (p < 0.03). We also observed increased BCAN expression with astrocytes in children with ASD, together with altered astrocyte morphology. Our results point to alterations in immune system signaling, glia cell differentiation, and synaptic signaling in the hippocampus of children with ASD, together with alterations in extracellular matrix molecules. Furthermore, our results demonstrate altered expression of genes implicated in genetic studies of ASD including SYN1 and MEF2C.
(© 2024. The Author(s).)
Databáze: MEDLINE
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